Cerebrovascular Effects Of Intrauterine Hypoxia: Contribution To Perinatal Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$579,138.00
Summary
During pregnancy, delivery of oxygen and nutrients to the growing fetus is sometimes disturbed, and can lead to injury of the developing brain. In this project we investigate the idea that low oxygen (hypoxia) causes brain demage to blood vessels in the fetal brain, and new blood vessesl produced in an attempt to repair this damage are fragile and prone to rupture, explaining the high incidence of bleeding in the brain of prematurely-born and full term infants that experience birth hypoxia.
Role Of Microparticles In Cardiac Ischemia Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$55,575.00
Summary
Interventional cardiology has reduced the mortality rate associated with heart attack, unfortunately the prevalence of heart failure has subsequently increased, caused in part by reperfusion injury of previously occluded vessels. We aim to identify novel insights into the pathogenesis of IR injury in the heart, as well as the development of new approaches to prevent cardiac damage during cardiac surgery, transplantation, post-angioplasty and coronary artery stenting.
Investigating The Mechanisms That Increase Nerve-evoked Vasoconstriction Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$372,547.00
Summary
People with spinal cord injury not only lose control of their arms and legs but also lose control of their bladder and bowel. They also have poor control of blood pressure and an overfull bladder or bowel can lead to dangerously high blood pressure. In this project, we are investigating how this abnormal high blood pressure is generated. The aim is to develop treatments which target the mechanisms which increase the blood pressure responses elicited by the bladder and bowel.
Therapeutic Approaches To Circumvent NO• Resistance In The Type 2 Diabetic Heart And Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$563,337.00
Summary
Type 2 diabetes (T2D) is Australia’s fastest growing chronic disease, affecting almost 2 million Australians (who face poor cardiovascular health outcomes). We have discovered an exciting new avenue that may potentially more effectively counteract heart and blood vessel disorders in T2D patients in an acute cardiovascular emergency, of substantial clinical importance.
Do Postjunctional Alterations Explain The Effects Of Diabetes On Neurovascular Transmission?
Funder
National Health and Medical Research Council
Funding Amount
$390,886.00
Summary
Diabetes produces disordered skin blood flow that increases risk of skin ulcers and gangrene. The project investigates nervous control of skin blood vessels in diabetes. It is assumed that all affects of diabetes on nerve function are explained by loss of nerves. We hypothesize that some affects of diabetes are due to dysfunction of blood vessels and not to nerve loss. The objective is to identify drug targets to improve blood flow in skin and thereby reduce the risk of skin ulcers and gangrene.
Peripheral Mechanisms Involved In Autonomic Hyperreflexia
Funder
National Health and Medical Research Council
Funding Amount
$229,917.00
Summary
Bladder distension or minor unheeded injuries below the lesion in spinally injured people often lead to episodes of high blood pressure that may cause stroke or death. These events require emergency hospitalization and are expensive as well as dangerous. After spinal injury, the control of sympathetic nerves that supply arteries and regulate blood pressure is lost. However, the nerves below the injury remain in place and the spinal cord below the lesion contains connections that can activate the ....Bladder distension or minor unheeded injuries below the lesion in spinally injured people often lead to episodes of high blood pressure that may cause stroke or death. These events require emergency hospitalization and are expensive as well as dangerous. After spinal injury, the control of sympathetic nerves that supply arteries and regulate blood pressure is lost. However, the nerves below the injury remain in place and the spinal cord below the lesion contains connections that can activate them. Signals from the bladder or skin enter the remaining lower part of the spinal cord and activate the sympathetic supply generating a rise in blood pressure. This project will test the hypothesis that increased sensitivity of arteries to the chemicals released from the sympathetic nerves leads to excessive vessel constriction, contributing to the exaggerated increase in pressure. We will investigate arteries removed from rats with experimental spinal transection. We will test the contractions of the arteries (a) to sympathetic nerve stimulation and (b) to the chemicals noradrenaline, adenosine 5'-triphosphate (ATP) and neuropeptide Y that are normally released during nerve activity. We will determine whether release of noradrenaline and ATP from nerves is normal or augmented using electrochemical and electrophysiological techniques. We will compare the responses with those in normal arteries, those in arteries whose nerves have been silenced by removing all connections from the spinal cord and those in arteries that have lost all their nerve supply. This will enable us to identify whether the mechanisms for release of transmitter substances are modified and whether the arterial muscle is hypersensitive to these substances. The results will help in the design of safer treatment for these potentially lethal emergencies in spinal patients.Read moreRead less
Regulation Of Bone Marrow Progenitor Cells For Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$442,930.00
Summary
Diabetic retinopathy (DR) is the leading cause of blindness in the working population of developed countries. Current treatments cannot restore the retinal vascular damage in DR. This project intends to combat DR by repairing the damaged retinal vasculature through short- and long-term regulations of the function of bone marrow derived endothelial progenitor cells. Success in this project would potentially have a major impact on all diabetic vascular complications.
Mechanisms Underlying Disordered Skin Blood Flow Following Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$408,000.00
Summary
Many people who recover from traumatic injury or who have chronic conditions such as diabetes or neuropathy from exposure to a toxic chemical suffer from peripheral vascular disorders leading to poor circulation in the extremities. These conditions are characterised by impaired wound healing, cold hands and feet and ongoing pain. These people must face a long life with progressively increasing disability. Even normal ageing can lead to similar problems. This project is directed at understanding ....Many people who recover from traumatic injury or who have chronic conditions such as diabetes or neuropathy from exposure to a toxic chemical suffer from peripheral vascular disorders leading to poor circulation in the extremities. These conditions are characterised by impaired wound healing, cold hands and feet and ongoing pain. These people must face a long life with progressively increasing disability. Even normal ageing can lead to similar problems. This project is directed at understanding the role of the nerve supply to blood vessels in the skin in these disorders. The experiments will be conducted in skin blood vessels of rats with various forms of nerve lesion that will mimic these conditions in patients. We will use our knowledge of the structure and behaviour of nerve-blood vessel connections to analyse the changes in the properties of vascular smooth muscle and relate it to the state of the innervation. Skin arteries normally receive two types of nerve - sympathetic (which release noradrenaline) and afferent ( which release peptides) - that have opposing actions on the vessel (constriction and dilation respectively). We hypothesize that removal of part or all of the innervation changes the contractile mechanism of the smooth muscle in the wall of the vessel so that it becomes much more sensitive to calcium ions and produces larger and more prolonged contractions. We will combine electrophysiology and contraction studies with immunohistochemistry and biochemical analysis to define the relation between the nerve deficit and the vascular responses. The aim is to identify appropriate drug targets for which local application in the affected region can alleviate the symptoms without causing widespread side effects.Read moreRead less
Complement Regulation: Protection Against Xenograft Rejection, Ischaemia And Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$256,980.00
Summary
Organ transplantation is an accepted solution to treat kidney, heart, lung and liver failure, and is being keenly sought for diabetes treatment. With refined surgical techniques and better controlled immunosuppression, the expected graft survival times are in years. However, the number of individuals who would benefit from transplants exceeds the supply of donor organs, and this number will increase as the benefits of having a transplanted organ increase. There is an active program to research t ....Organ transplantation is an accepted solution to treat kidney, heart, lung and liver failure, and is being keenly sought for diabetes treatment. With refined surgical techniques and better controlled immunosuppression, the expected graft survival times are in years. However, the number of individuals who would benefit from transplants exceeds the supply of donor organs, and this number will increase as the benefits of having a transplanted organ increase. There is an active program to research the possibility of using animal organs (xenografts). This project addresses one of the many issues arising from xenograft transplantation - the rapid activation of the body's complement system, which without treatment results in the very rapid rejection of the graft. In principle this problem can be solved by the development of transgenic donor animals that carry one or more human genes that produce a complement regulating protein, such as CD46 (MCP) or CD55 (DAF). In practice, however, to get successful longterm organ function still requires the selection of the optimal complement regulator or combination of regulators and an understanding of how they function. This research work analyses how CD46 and CD55 function to protect tissues from complement activation, and will result in selection of appropriate transgenes for xenografting. Another aspect of transplantation that is addressed in this proposal is the damage that a graft suffers when the blood supply is temporarily removed during organ harvest and the grafting procedure. This is similar to what occurs during a heart attack when a portion of heart muscle is starved of blood: as the blood flows again through the tissue there is a powerful reaction, again involving complement activation, which is known as reperfusion injury. We have found that perfusing a graft with a soluble form of the CD46 complement regulator provides protection against this damage. The research will measure and optimise this protection.Read moreRead less